1. Field of the Invention
The present invention relates, in general, to a novel transport protein, IT10C3. In particular, the present invention relates to nucleic acid molecules coding for IT10C3; IT10C3 polypeptides; recombinant nucleic acid molecules; cells containing the recombinant nucleic acid molecules; antisense IT10C3 nucleic acid constructs; antibodies having binding affinity to an IT10C3 polypeptide; hybridomas containing the antibodies; nucleic acid probes for the detection of IT10C3 nucleic acid; a method of detecting IT10C3 nucleic acid or polypeptide in a sample; and kits containing nucleic acid probes or antibodies.
2. Background Information
Huntington's disease (HD) is a familial neurodegenerative disorder that afflicts about 1/10,000 individuals (Martin, J. B. and Gusella, J. F., N. Engl. J. Med. 315:1267-1276 (1986); Gusella, J. F., Adv. Hum. Genet. 20:125-151 (1991)). It is inherited in an autosomal dominant manner and is characterized by choreiform movements, dementia, and cognitive decline. The disorder usually has a mid-life onset, between the ages of 30 to 50 years, but may in some cases begin very early or much later in life. The symptoms are progressive and death ensues 10 to 20 years after onset, most often as the result of secondary complications of the movement disorder. Post-mortem examination of the brains of HD individuals has revealed a selective loss of neurons that most dramatically affects the striatum. The biochemical cause of this neuronal loss which underlies the symptoms of HD has not yet been discovered. Thus, an intensive effort has been mounted to apply location cloning techniques to identify the nature of the genetic defect.
The HD gene has been mapped to a 2.2 Mb region, flanked by the loci D4S126 and D4S98 in the terminal cytogenetic subband of the short arm of human chromosome 4 (MacDonald, M. E. et al., Neuron 3:183-190 (1989); Bates, G. P. et al., Am. J. Hum. Genet. 49:7-16 (1991); Snell, R. G. et al., Am. J. Hum. Genet. 51:357-362 (1992)). Analysis of linkage disequilibrium on HD chromosomes has revealed that the disorder is associated with a wide array of marker haplotypes, but has suggested a 500 kb segment of the candidate region between D4S180 and D4S182 as the most probable location of the genetic defect (MacDonald, M. E. et al., Nature Genet. 1:99-103 (1992)). The task of isolating all the transcripts from the candidate region remains a daunting one, despite the availability of cloned genomic DNA (Lin, C. S. et al., Somat. Cell Mol. Genet. 17:481-488 (1991); Bates, G. P. et al., Nature Genetics 1:180-187 (1992)). However, the recent development of the "exon amplification" technique, which targets the isolation of potential coding regions from cloned genomic DNA, may be used to search for candidate genes (Buckler, A. J. et al., Proc. Natl. Acad. Sci. USA 88:4005-4009 (1991)). A novel G protein-coupled receptor kinase and the human .alpha.-adducin gene (ADDA) were previously identified by applying this procedure to the region between D4S127 and D4S182 in the HD candidate region (Ambrose, C. et al., Hum. Mol. Genet. 1:697-703 (1992); Taylor, S. A. M. et al., Nature Genet. 2:223-227 (1992)). The present invention provides a second gene within the same cosmid as the ADDA locus. This novel gene encodes a protein with strong amino acid sequence similarity to a superfamily of transporters typified by tetracycline resistance proteins (Marger, N. D. and Saier, M. H. Jr., TIBS 18:13-20 (1993)).